Safety of beta-blocker discontinuation in patients after acute coronary syndromes and preserved left ventricular ejection fraction: long-term clinical outcomes from the SPUM-ACS cohort

Abstract Background While beta-blockers have been shown to improve outcomes after acute coronary syndromes (ACS), most trials predate the advent of reperfusion therapy and modern secondary prevention. Recent trial data in the reperfusion era found no all-cause or cardiovascular mortality benefit in patients with a left ventricular ejection fraction (LVEF) >40%, while myocardial infarction and angina were reduced. We hypothesized that, in patients who receive optimal contemporary treatment following ACS and who have an LVEF >40%, beta-blocker discontinuation within 1 year after ACS is safe and non-inferior to beta-blocker continuation in terms of the 5-year incidence of major adverse cardiovascular events (MACE). Purpose We assessed the safety of beta-blocker discontinuation within 12 months following ACS in patients with an LVEF >40% at discharge, compared to continued long-term beta-blocker therapy, with respect to the 5-year incidence of MACE. Methods Data was derived from the Swiss Special Program University Medicine – Inflammation in ACS (SPUM-ACS) cohort (N=3,762), a multicenter prospective cohort of patients hospitalized for invasive management of ACS between 2009-2017. We included patients with an LVEF >40%, beta-blockers at discharge, and who completed the 5-year follow-up. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers at any time throughout the first year after ACS using a target trial emulation design. Adjusted hazard ratios (aHR) were obtained with a Cox model using an inverse probability weighting adjustment for baseline characteristics including demographic parameters, comorbidities, and concomitant medication. The primary endpoint was 5-year MACE (cardiovascular death, myocardial infarction, stroke or transient ischemic attack, unplanned coronary revascularization, and hospitalization for unstable angina). Results Of 2,077 patients with an LVEF >40% and beta-blockers at discharge, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blocker therapy at one year. The 5-year risk between the discontinuation and continuation group was similar for the primary endpoint (14.5% vs 14.3%, respectively, aHR 1.00, 95%CI 0.73-1.36, p=0.98). All-cause mortality (aHR 1.08, 95%CI, 0.64-1.81, p=0.79) did not differ between both groups. In a subgroup analysis, there was no effect modification by LVEF, but some evidence for a higher risk of primary endpoint with beta-blocker discontinuation in STEMI (aHR 1.50, 95%CI 1.02-2.21) compared with NSTEMI (aHR 0.69, 95%CI 0.40-1.19, P interaction = 0.022). Conclusion Beta-blocker discontinuation within 12 months following ACS in patients with an LVEF >40% was not associated with an increased risk of MACE at 5 years, compared to long-term continuation of beta-blocker therapy. In the absence of a dedicated randomized controlled trial, beta-blocker discontinuation may be safe, especially after NSTEMI.Kaplan-Meier plot: probability of MACE